KMID : 0620920090410080538
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Experimental & Molecular Medicine 2009 Volume.41 No. 8 p.538 ~ p.547
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Protective effect of total aralosides of Aralia elata (Miq) Seem (TASAES) against diabetic cardiomyopathy in rats during the early stage, and possible mechanisms
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Xi Shugang
Zhou Guihua Zhang Xuexin Zhang Wenjie Cai Lu Zhao Chunyan
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Abstract
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Total aralosides of Aralia elata (Miq) Seem (TASAES) from Chinese traditional herb Longya Aralia chinensis L was found to improve cardiac function. The present study was to determine the protective effects of TASAES on diabetic cardiomyopathy, and the possible mechanisms. Therefore, a single dose of streptozotocin was used to induce diabetes in Wister rats. Diabetic rats were immediately treated with low, medium and high doses of TASAES at 4.9, 9.8 mg/kg and 19.6 mg/kg body weight by gavage, respectively, for eight weeks. Cardiac function was evaluated by in situ hemodynamic measurements, and patch clamp for the L-type Ca2+ channel current (ICa2¡¾L) and transient outward K+ channel current (Ito). Histopathological changes were observed under light and electron microscope. The expression of pro-fibrotic factor, connective tissue growth factor (CTGF) was monitored using immunohistochemistry staining. Compared with diabetic group, medium and high doses, but not low dose, of TASAES showed a significant protection against diabetes-induced cardiac dysfunction, shown by increased absolute value of left ventricular systolic pressure (LVSP) and maximum rates of pressure development (¡¾dp/dtmax), and enhanced amplitude of ICa2¡¾L (P < 0.05). Histological staining indicated a significant inhibition of diabetes-caused pathological changes and up-regulation of CTGF expression (P < 0.05). The results suggest that TASAES prevents diabetes- induced cardiac dysfunction and pathological damage through up-regulating ICa2¡¾L in cardiac cells and decreasing CTGF expression.
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KEYWORD
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araloside, calcium channels, L-type, cardiomyopathies, connective tissue growth factor, diabetes mellitus, heart, hemodynamics, myocardium
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